Screening and validation of blood composite markers for diagnosing prostate cancer
10.3760/cma.j.cn112330-20241210-00549
- VernacularTitle:诊断前列腺癌的血液复合标志物的筛选和验证
- Author:
Kang LIU
1
;
Kaiwen FENG
1
;
Dongrong YANG
1
;
Jin ZHU
1
Author Information
1. 苏州大学附属第二医院泌尿外科,苏州 215004
- Publication Type:Journal Article
- Keywords:
Proteomics;
Prostatic neoplasms;
Carcinoma;
Early diagnosis;
Biomarker
- From:
Chinese Journal of Urology
2025;46(6):447-454
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the diagnostic efficacy of differentially expressed proteins in the plasma of prostate cancer patients.Methods:Plasma samples were collected from patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from January to March 2023. Among them,there were 30 patients with prostate cancer,aged(75.10 ± 9.33)years,with a median serum PSA value of 24.60(5.38,516.00)ng/ml,and 30 patients with benign prostatic hyperplasia,aged(72.90 ± 7.30)years,with a median serum PSA value of 2.21(0.44,4.38)ng/ml Label-free quantitative proteomic technology was used to detect differentially expressed proteins in the plasma. Combined with TCGA transcriptome changes and relevant literature,the differentially expressed candidate proteins with the most significant up-regulation were selected.In addition,prostate biopsy tissue samples were collected from another 14 patients who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from September to November 2023. Among them,there were 8 patients with prostate cancer,aged(72.25 ± 6.52)years,with a median serum PSA value of 74.65(5.63,151.00)ng/ml,and 6 patients with benign prostatic hyperplasia,aged(70.83 ± 5.04)years,with a median serum PSA value of 5.06(3.34,28.70)ng/ml. Immunohistochemical staining was performed using antibodies corresponding to the candidate proteins to analyze the expression differences of the candidate proteins between the 8 prostate cancer cases and the 6 benign prostatic hyperplasia cases.Plasma samples were collected from 44 patients with prostate diseases who visited the Department of Urology at the Second Affiliated Hospital of Soochow University from March to September 2023. Among them,there were 30 patients with prostate cancer,aged(71.58 ± 7.99)years,with a median serum PSA value of 29.85(1.25,108.00)ng/ml,and 14 patients with benign prostatic hyperplasia,aged(69.00 ± 8.94)years,with a median serum PSA value of 1.78(0.61,12.40)ng/ml. Area under the curve(AUC)was calculated to analyze the diagnostic efficacy of each protein for prostate cancer. Detect the expression levels of candidate proteins in plasma by ELISA,draw the ROC curve,calculate the area under the curve(AUC),and analyze the diagnostic efficacy of each protein for prostate cancer.Results:A total of 34 most significant upregulated proteins and 72 downregulated proteins were detected by proteomics and eight proteins were detected by referring to TCGA data and literatures. Percentage of positive cells of SPON2,FGB,PCSK6,ORM1,ORM2,HP,SND1,and SUSD2 in prostate cancer tissues(51.97 ± 10.81,42.97 ± 6.76,49.83 ± 12.46,53.85 ± 11.52,50.46 ± 11.13,39.69 ± 10.96,52.01 ± 13.03,45.92 ± 9.55)were significantly higher than in BPH(36.31 ± 19.87,21.85 ± 10.99,21.59 ± 5.61,20.36 ± 4.75,24.38 ± 11.55,20.75 ± 3.75,23.60 ± 6.51,19.69 ± 8.45)( P < 0.05). FGB,HP,and ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients(ng/ml)[(689.9 ± 659.7)ng/ml vs.(200.0 ± 127.1)ng/ml,(1.819 ± 0.833)ng/ml vs.(1.126 ± 0.362)ng/ml,(733.5 ± 385.0)ng/ml vs.(344.7 ± 214.6)ng/ml, P < 0.05],with AUC values 0.803,0.781,and 0.832,respectively. The combined diagnostic efficacy of the three proteins FGB,HP,and ORM1 for prostate cancer is significantly better than that of any single protein(AUC = 0.953),with higher sensitivity(81.48%)and specificity(100.0%). Conclusions:FGB,HP,ORM1 were significantly increased in plasma of prostate cancer patients compared to BPH patients,indicating higher diagnostic efficacy. The combined diagnostic efficacy FGB,HP,and ORM1 for prostate cancer is significantly better than that of any single protein,and they exhibit higher sensitivity and specificity.